Mitogenic activity of staphylococcal peptidoglycan

Dziarski, Roman; Dziarski, Agnes

doi:10.1128/iai.23.3.706-710.1979

Cited by 40 publications

(19 citation statements)

References 8 publications

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“…the major constituent of the cell wail, exerts several immunostimulatory effecls. including B-ceil miiogenicity [7] and polyclonai activation [8], adjuvancy [6, i3], and stimulation of the reticuloendotheiiai system. In the present study, we tested potential adjuvant properties of S. mutans PG for enhancement of immune responses to orally administered TNP-S. mutans.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of Murine Immune Responses to Orally Administered Haptenated Streptococcus mutans

et al. 1982

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The induction of immune responses to orally administered trinitrophenyl (TNP)-haptenated Streptococcus mutans and its enhancement with muramyldipeptide (MDP), peptidoglycan (PG), and concanavalin A (Con A) were investigated in lipopolysaccharide (LPS)-non-responsive C3H/HeJ mice and the syngeneic, LPS-responsive C3H/HeN strain. Both mouse strains manifested similar immune responses, primarily of the IgM isotype, after a single gastric intubation (GI) with TNP-S. mutans. However, when groups of animals were first carrier-primed by GI with S. mutans for 2 consecutive days, followed by a single GI with TNP-S. mutans 1 week later, C3H/HeJ mice gave a significantly higher (P less than or equal to 0.01) splenic IgA anti-TNP plaque-forming cell (PFC) response than identically treated C3H/HeN mice. Furthermore, saliva, urine and serum from these C3H/HeJ mice possessed high levels of IgA anti-TNP antibodies as determined by the enzyme-linked immunosorbent assay, whereas C3H/HeN mice exhibited low antibody levels. Oral administration of Con A (either 250 micrograms or 500 micrograms/mouse) or purified PG (1 mg/mouse) at the time of TNP-S. mutans immunization resulted in significantly (P less than or equal to 0.01) enhanced splenic IgA anti-TNP PFC responses, especially in C3H/HeJ mice. On the other hand, MDP promoted IgA anti-TNP PFC responses in LPS-responsive C3H/HeN mice but did not augment responses in C3H/HeJ animals. A similar immune response pattern was seen when antibody levels were measured in serum, saliva, and urine of both mouse strains. These results demonstrate that haptenated S. mutans is a good antigen for the induction of high IgA responses in orally immunized C3H/HeJ mice and that this high response can be enhanced with the adjuvants Con A and PG. However, MDP is ineffective in C3H/HeJ mice but enhances IgA responses in normal LPS-responsive C3H/HeN animals.

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Section: Discussionmentioning

confidence: 99%

Enhancement of Murine Immune Responses to Orally Administered Haptenated Streptococcus mutans

et al. 1982

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“…Analysis of the chemical composition of PG revealed the presence of lysine, glutamic acid, glycine, alanine, glucosamine, and muramic acid (12), indicating no significant contamination with teichoic acid, proteins, nucleic acids, or other cell components. Accidental contamination with exogenous endotoxins was ruled out by toxicity tests in adrenalectomized mice (10). Before use, PG was suspended in sterile phosphatebuffered saline, treated with ultrasonication for 1 h (11), and then heated at 70°C for 1 h and tested for sterility.…”

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confidence: 99%

“…Staphylococcal cells and cell wall products have received particular attention in studies of human lymphoid cells (10,11,13,17,21,25,30). Most of these studies were performed with Staphylococcus aureus Cowan I, which is a strain with exceptionally high protein A content, or with purified protein A.…”

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confidence: 99%

“…They have suggested that protein A is largely responsible for the lymphocyte-activating properties of staphylococcal cells. Recently, we have demonstrated the mitogenic activity of staphylococcal peptidoglycap (PG), a heteropolymer which is the major constituent of the cell wall of gram-positive bacteria, and also of protein-free cell wall (tei-choic acid-PG complex) (10,11). In mice, PG is a T-cell-independent B-lymphocyte mitogen (8,10), and it is also a potent inducer of polyclonal immunoglobulin secretion (9).…”

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confidence: 99%

“…In general, studies in man have been limited to our investigation of proliferative responses of unfractionated lymphocytes to PG from peripheral and cord blood (10,11). Recently, these studies were extended by Rasanen and Arvilommi (26) who demonstrated mitogenic activity of staphylococcal cell wall and PG for isolated human T and B lymphocytes.…”

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Staphylococcal peptidoglycan: T-cell-dependent mitogen and relatively T-cell-independent polyclonal B-cell activator of human lymphocytes

Levinson¹,

Dziarski²,

Zweiman³

et al. 1983

Infect Immun

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Staphylococcal cell wall products have been widely examined as probes for dissection of in vitro human immune responses. Mitogenic and polyclonal B-cellactivating properties have been attributed to intact cell walls or the protein A constituent thereof. We now report that staphylococcal peptidoglycan (PG), the major cell wall constituent, is not only a potent mitogen but also a polyclonal Bcell activator for human peripheral blood mononuclear cells (PBM). PG-induced proliferative responses of human PBM were comparable to that observed in pokeweed mitogen-stimulated cultures. As was true for pokeweed mitogen, PGinduced proliferation required the presence of T-cell help. Cultures of human PBM with PG also resulted in B-cell differentiation as reflected by an increase in numbers of immunoglobulin-secreting cells in stimulated cultures. In contrast to the proliferative response, PG-induced B-cell differentiation was relatively T-cell independent. This point became apparent when B-cell fractions were partially depleted of excessive numbers of monocytes before culture. Also, B-cell proliferation did not appear to be a major prerequisite for PG-induced B-cell differentiation responses. These data indicate that PG is a potent T-cell-dependent mitogen and relatively T-cell-independent polyclonal B-cell activator of human lymphocytes.

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Correlation between ribosylation of pertussis toxin substrates and inhibition of peptidoglycan‐, muramyl dipeptide‐ and lipopolysaccharide‐induced mitogenic stimulation in B lymphocytes

Dziarski

1989

Eur J Immunol

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Selective inhibition by pertussis toxin (PT) of mitogenic activation of mouse B lymphocytes by bacterial mitogens (peptidoglycan and lipopolysaccharide) and muramyl dipeptide (a synthetic analog of peptidoglycan fragment) was demonstrated. Mitogenic activation of B cells by protein kinase C activators and ionomycin was insensitive to PT. Also PT did not inhibit peptidoglycan- and lipopolysaccharide-induced differentiation of B cells into Ig-secreting cells, when it was added to the cultures after the proliferative stage of the response. B lymphocyte membranes contained two major PT substrates (40 and 41 kDa). The extent of PT-mediated ADP ribosylation of these substrates correlated with the degree of PT-mediated inhibition of mitogenic stimulation of B cells. B cell stimulation by all mitogens tested was not inhibited by cholera toxin at nontoxic concentrations that are known to cause maximal increase in cAMP in B cells. Since the only known substrates for PT-mediated ADP ribosylation in mammalian cells are the alpha subunits of some G proteins, our data suggest that G proteins are present in B cell membranes and that they are involved in B cell activation induced by bacterial mitogens.

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Mitogenic activity of staphylococcal peptidoglycan

Cited by 40 publications

References 8 publications

Enhancement of Murine Immune Responses to Orally Administered Haptenated Streptococcus mutans

Enhancement of Murine Immune Responses to Orally Administered Haptenated Streptococcus mutans

Staphylococcal peptidoglycan: T-cell-dependent mitogen and relatively T-cell-independent polyclonal B-cell activator of human lymphocytes

Correlation between ribosylation of pertussis toxin substrates and inhibition of peptidoglycan‐, muramyl dipeptide‐ and lipopolysaccharide‐induced mitogenic stimulation in B lymphocytes

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